Hemisynthesis, Antitumoral Effect, and Molecular Docking Studies of Ferutinin and Its Analogues
Hemisynthesis, Antitumoral Effect, and Molecular Docking Studies of Ferutinin and Its Analogues
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Ferutinin及其类似物的半合成、抗肿瘤作用及分子对接研究
DOI：
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发表时间：
2016
影响因子：
3
通讯作者：
E. Delfourne
中科院分区：
文献类型：
--
作者：
R. Safi;F. Rodriguez;G. Hilal;M. Diab‐Assaf;Y. Diab;M. El;F. Najjar;E. Delfourne
天然产物ferutinin是雌激素受体ERα的激动剂和ERβ的激动剂/拮抗剂，对乳腺癌细胞具有较弱的抗增殖活性。为了提高这一活性，ferutinin类似物合成jaeschkenadiol与不同的酸酯化。测定这些化合物对雌激素依赖性（MCF-7）和雌激素非依赖性（MDA-MB-231）乳腺癌细胞系的体外抗增殖活性。其中化合物3c'对MCF-7具有较强的选择性抑制活性，IC 50值为1 μm。ER的配体结合结构域中3c'的对接模拟表明与两种ER亚型的潜在拮抗相互作用。功能分析表明，3c'是ERα蛋白的拮抗剂，而ferutinin是ERα蛋白的激动剂。
The natural product ferutinin was shown to act as an agonist to estrogen receptor ERα and agonist/antagonist to ERβ featuring a weak antiproliferative activity toward breast cancer cells. To enhance this activity, ferutinin analogues were synthesized by esterification of jaeschkenadiol with different acids. These compounds were assayed for their in vitro antiproliferative activity against estrogen‐dependent (MCF‐7) and estrogen‐independent (MDA‐MB‐231) breast cancer cell lines. Among the compounds, 3c’ exhibited a potent inhibitory selective activity against MCF‐7 with IC50 value of 1 μm. Docking simulation of 3c’ in the ligand binding domain of the ERs indicated a potential antagonism interaction with both ER subtypes. Functional assay showed that 3c’ binds as an antagonist to ERα protein while ferutinin acts as an agonist.